title: Effects of alcohol consumption on antigen-specific cellular and humoral immune responses to SIV in rhesus macaques.
abstract: BACKGROUND
  Simian immunodeficiency virus (SIV) infection in macaques chronically receiving ethanol results in significantly higher plasma viral loads and more rapid progression to end-stage disease. We thus hypothesized that the increased plasma viral load in ethanol-treated, SIV-infected macaques would negatively correlate with antigen-specific immune responses.
  
  
  METHODS
  Rhesus macaques were administered ethanol or sucrose (n = 12 per group) by indwelling gastric catheters for 3 months and then intravenously infected with SIVMAC251. Peripheral blood T- and B-cell immunophenotyping and quantification were performed. Plasma was examined for viremia, levels of SIVEnv-specific binding, and neutralizing antibodies. Virus-specific interferon γ and tumor necrosis factor α cytokine responses to SIV-Nef, Gag, or Env peptide pools were measured in peripheral blood CD8 T cells.
  
  
  RESULTS
  Macaques receiving ethanol had both higher plasma viremia and virus-specific cellular immune responses compared with the sucrose-treated group. The emergence of virus-specific cytokine responses temporally correlated with the decline in mean plasma viral load after 14 days postinfection in all SIV-infected animals. However, neither the breadth and specificity nor the magnitude of virus-specific CD8 T-cell responses correlated with early postpeak reductions in plasma viral loads. In fact, increased cytokine responses against Gag, gp120, and gp41 positively correlated with plasma viremia. Levels of SIV envelope-specific immunoglobulin G and neutralizing antibodies were similar over the disease course in both groups of macaques.
  
  
  CONCLUSIONS
  Persistently higher antigen-specific cytokine responses in animals receiving ethanol are likely an effect of the higher viral loads and antigen persistence, rather than a cause of the increased viremia.
authors.affiliation: *Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA; Departments of †Physiology; ‡Medicine, Louisiana State University Health Sciences Center, New Orleans, LA; and §Department of Surgery, Michigan State University College of Human Medicine, East Lansing, MI.
authors.forename: Bapi
authors.initials: B
authors.lastname: Pahar
authors.forename: Angela M
authors.initials: AM
authors.lastname: Amedee
authors.forename: Jessica
authors.initials: J
authors.lastname: Thomas
authors.forename: Jason P
authors.initials: JP
authors.lastname: Dufour
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Steve
authors.initials: S
authors.lastname: Nelson
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bagby
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects*; D056724:Immunity, Humoral / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus; D019562:Viral Load
chemical_list: D016207:Cytokines